Sweat test or pilocarpine iontophoresis test is the existing method for diagnosis of cystic fibrosis that is recommended to perform at 48 hours after birth. However, the current method is painful, with several side effects such as full thickness skin burn, skin rash, erythema etc. Therefore, the purpose of this study is to develop a pilocarpine topical formulation which can stimulate sweat secretion when applied on skin without iontophoresis. Several formulations with TranscutolRTM, polyethylene glycol 400 (PEG 400), Polyethylene glycol 200 (PEG 200), menthol and salicylic acid (SA) each at varying concentrations were screened as penetration enhancers. In vitro penetration test (IVPT) was performed on these formulations to compare the influence of these ingredients on the penetration of pilocarpine. The results from the preliminary studies indicate that the formulation with SA showed better penetration into porcine skin after both 10 minutes (120.29 +/- 27.54 mug/cm2) and 40 minutes (158.97 +/- 20.15 mug/cm2) compared to others. Based on the preliminary studies, the lead formulation was decided to have pilocarpine nitrate, ethanol and water as solvents, salicylic acid as penetration enhancer, PEG 200 as a hydrating agent to minimize any dehydration due to ethanol, menthol as a cooling agent and sodium hydroxide as a pH modifier. The penetration of pilocarpine nitrate on application of lead formulation into the porcine skin was compared to that of iontophoresis technique by both IVPT as well as tape stripping techniques. The IVPT results indicate that total amount of pilocarpine nitrate recovered from skin with passive formulation (152.04 +/- 52.23 mug/cm2 after 10 min, 210.27 +/- 53.72 mug/cm2 after 40 min) is higher than that of iontophoresis with pilocarpine solution (97.05 +/- 27.93 mug/cm2 after 10 min, 140.56 +/- 88.66 mug/cm2 after 40 min) at both 10 and 40 minutes. The tape stripping data showed a correlation with the IVPT results. The amount of pilocarpine recovered from the tape strips used in the lead formulation (78.46 mug/mg at 10 min and 53.32 mug/mg at 40 min) was significantly higher than the pilocarpine recovered from tape strips used for iontophoresis (13.32 mug/mg at 10 minute and 7.38 mug/mg at 40 minutes). The lead formulation was also investigated for its effectiveness by a clinical study on 20 human volunteers to determine if the developed formulation was efficient enough to stimulate the sweat production. The average amount of the sweat secreted due to passive formulation was found to be 77.28 +/- 18.97 mg when applied on an area of 38.46 cm2. Based on these results, it can be concluded that the passive formulation was successful in delivering pilocarpine and to stimulate sweat secretion which can be a compliant alternative technique to iontophoresis.