Clinical observations have suggested that wound healing may be altered in patients treated with systemic isotretinoin. In this study, we examined the effects of systemic isotretinoin on dermal wound healing and connective tissue metabolism in a rabbit ear model. Forty 6-mm punch-biopsy wounds were created in the ears of two control rabbits as well as two experimental animals fed isotretinoin, 4 mg/kg per day. Clinical inspection and histologic examination revealed no difference between the control and isotretinoin-treated rabbits in terms of the time required for complete wound healing or the appearance of the final scar. The tissue removed from the wound site at days 0, 7, 14, and 21 after wounding was subjected to analysis of a collagen production and collagen gene expression. Collagen production, determined by the synthesis of [3H]hydroxyproline after incubation of tissue slices with [3H]proline in vitro or by the measurement of the steady-state levels of types I and III procollagen mRNAs, was not significantly different between the two groups. The results indicate that systemic administration of isotretinoin does not affect collagen synthesis in the rabbit ear model of wound healing.