This double-blind, vehicle-controlled, multicenter study evaluated the efficacy and safety of a new topical antineoplastic agent, masoprocol, in the treatment of actinic keratoses of the head and neck. Of the 113 patients who applied topical masoprocol twice a day for 14 to 28 days, there was a mean decrease in actinic keratoses from 15.0 to 5.4 and a median percent reduction from baseline actinic keratosis count of 71.4% at the 1-month follow-up visit. Comparable numbers for the vehicle-treated group were 13.4 to 11.1 actinic keratoses and 4.3% median percent reduction. Irritation, as manifested by erythema or flaking, occurred in 61.5% of topical masoprocol-treated patients versus 26.7% of those treated with vehicle and did not correlate with clinical response. Topical masoprocol appears to be useful in the treatment of actinic keratoses.