Five groups of 12 healthy volunteers each received in double-blind, randomized fashion oral b.i.d. doses of 10, 20, or 40 mg loratadine, 12 mg chlorpheniramine maleate (CTM), or placebo for 28 days. Histamine and saline were injected intradermally into opposite arms at baseline and at specified times following treatment on days 1, 3, 7, 14, 21, and 28. Notable suppression of adjusted wheal formation (histamine-induced minus saline-induced) occurred within two hours after the first dose of each active treatment on day 1. In general, throughout the treatment period, suppression of adjusted wheal formation by all doses of loratadine was significantly greater than by placebo. Suppression by 10 mg loratadine was comparable to CTM, and 20 and 40 mg loratadine were significantly greater than CTM. Suppression of wheal formation by loratadine during the treatment period and during five days posttreatment were dose related. The continued effectiveness of loratadine throughout the 28 days suggests that tolerance to loratadine did not develop in this study. Sedation occurred in 8 of 12 subjects receiving CTM, 1 of 12 receiving 10 mg loratadine, and 1 of 12 receiving placebo.