The possible causative role of the yeastlike fungus Pityrosporum (Malassezia) orbiculare in the pathogenesis of seborrheic dermatitis in patients with and without acquired immunodeficiency syndrome (AIDS) has been discussed but not resolved. Ten patients with AIDS-related seborrheic dermatitis were studied for the presence of Pityrosporum organisms. On the basis of a quantitative correlation between numbers of yeast cells adherent to and extruded from keratinocytes and the clinical severity of seborrheic dermatitis, an association, if not a causative role, for Pityrosporum is strongly suggested in seborrheic dermatitis in patients with AIDS. This association was further strengthened by the marked clinical response to ketoconazole in two patients with a concomitant decrease in the number of Pityrosporum cells per keratinocyte.