The development of subsensitivity to first-generation H1 blockers often occurs within days or weeks of treatment. It is manifested by a decrease in efficacy and a waning of the inhibition of skin reactivity to allergen or histamine. Subsensitivity to loratadine was investigated in a double-blind, placebo-controlled parallel group study in 20 allergic subjects (22 to 35 years) who received either placebo or loratadine (10 mg one daily) for 12 weeks. Skin prick tests were done with six threefold increasing concentrations of standardized allergen extracts (orchard grass or mite) and histamine-coated Phazet. Skin tests were done before any treatment and after 7, 28, 56, and 84 days. Wheals and flares were measured. Compliance was monitored strictly during the study. Statistical analysis was done by parallel line bioassay and Wilcoxon W test. Skin test reactivity to histamine or allergen did not change throughout the trial in the placebo-treated group. Patients treated by loratadine had a significantly smaller wheal-and-flare reaction after 7 days. This effect was greater at 28 days and lasted throughout the treatment period. This study demonstrates that subsensitivity to loratadine measured by histamine and allergen skin tests does not develop during a 12-week period.