Six patients with persistent palmoplantar pustulosis were treated with acitretin, and the clinical response was compared with the effect on the intra-epidermal accumulation of polymorphonuclear PMN leukocytes. A prompt improvement of pustule formation and subsequently decreased scaling and erythema was seen in all patients. Following discontinuation of therapy, a relapse occurred within 2 weeks. With dosages of 45 or 55 mg/day, the clinical scores were only slightly better than with 25 or 35 mg/day. In patients using 25 mg acitretin a day, the leukotriene B4-induced intra-epidermal accumulation of polymorphonuclear leukocytes was not affected. However, a dosage of 35 mg/day resulted in a significant inhibition of PMN accumulation, dosages of 45 and 55 mg/day causing an even more pronounced inhibition of this process. Although the effect of different dosages of acitretin is not clearly expressed in the severity scores, the dose-dependent effect on PMN chemotaxis in vivo might be of relevance when combination therapies are considered, in order to achieve a complete clinical clearance.