The effect of oral isotretinoin (13-cis-retinoic acid) on in vivo chemotactic responses was studied longitudinally in 7 patients with cystic acne. As measured in a microchamber chemotaxis assay, both monocyte and neutrophil chemotaxis were inhibited 98% (p less than 0.001) during isotretinoin treatment. In vivo chemotactic responses returned to normal within 2 months of cessation of treatment. Biopsies of skin chamber sites from patients on isotretinoin showed no significant dermal or epidermal leukocytic accumulation in response to autologous zymosan-activated serum, whereas chambers from controls showed extensive neutrophilic infiltrates even in the epidermis. In contrast, in vitro chemotactic responses of neutrophils and monocytes from patients on isotretinoin were not diminished. Sera and plasma from patients on isotretinoin contained no inhibitors of chemotaxis, and activated sera from these patients were excellent attractants for normal monocytes. We postulate that isotretinoin produces significant anti-inflammatory effects by inhibition of monocyte and neutrophil chemotaxis across intact biologic barriers in vivo.