We studied the intraocular pressure (IOP)-lowering effect and the side effects of a new transdermal delivery system (TDS) containing pilocarpine. After giving their written informed consent, patients were randomly assigned to receive a pilocarpine TDS or a placebo TDS. Two patches, each containing 30 mg of pilocarpine or placebo, were applied to the supraclavicular skin of 24 patients. The IOP was recorded before and at +12, 16, and 20 h after application. Plasma samples were analyzed for pilocarpine before treatment and 12 and 20 h later via high-performance liquid chromatography. The amount of drug remaining on the dermal patches was analyzed at 20 h. The mean IOP recorded before application was 22.7 +/- 5.8 mmHg. As compared with the placebo TDS, the pilocarpine TDS did not significantly reduce IOP at 12, 16, or 20 h after application (P = 0.42). The mean plasma concentrations were 2.9 ng/ml at 12 h and 1.3 ng/ml at 20 h. The verum TDS showed a residual mean drug concentration of 35.3 mg pilocarpine on the TDS. A substantial amount of pilocarpine was released from the TDS to the dermis, causing detectable plasma levels of pilocarpine at 12 and 20 h after administration. The pilocarpine TDS is a new nonocular pharmaceutical device that should avoid the side effects well known in glaucoma treatment when conventional eye drops are used.