The ascomycin macrolactam derivative pimecrolimus is a novel, nonsteroidal, cell-selective inhibitor of inflammatory cytokines specifically developed for the treatment of inflammatory skin diseases. Our objective was to assess the efficacy, tolerability and safety of pimecrolimus cream 1% in the treatment of seborrheic dermatitis. Adults with seborrheic dermatitis of the face and upper trunk who were seen from October 2003 to April 2004 at the Dermatologic Outpatient Clinic of the University of Thrace were enrolled in this 9-week open-label uncontrolled study. Pimecrolimus cream 1% was applied as monotherapy twice daily for 7 days and for an additional period of 7 days thereafter, if needed, until complete clearance was achieved. In cases of recurrence a 5-day course was additionally applied. After screening and an appropriate washout period, subjects were evaluated at baseline (day 0) and at follow-up visits at weeks 1, 3, 6 and 9. The clinical severity of seborrheic dermatitis was estimated as mild (total score 1-3), moderate (total score 4-6) and severe (total score 7-9) in terms of erythema, scaling and lesional extent using a scale from 0 to 3 for each. Patients also assessed their symptoms on a scale from 0 to 5 in terms of the efficacy, safety and tolerability of topical application. Nineteen patients (12 males, seven females) were enrolled in this study. At the end of weeks 1, 3, 6 and 9 the percentages of complete clearance were 63%, 100%, 47% and 52%, respectively. At the end of the study, subjects' average assessment score was 9.73. Apart from topical burning and irritation of the skin in four patients, no other adverse event was mentioned. This pilot study indicates that pimecrolimus applied twice daily can be a safe and efficacious alternative in the treatment of seborrheic dermatitis. Further studies are needed to determine the initial and maintenance therapy.