Nitric oxide (NO) is a free radical synthesized from l-arginine by a family of NO synthase (NOS) enzymes, all of which are present in the skin, and also by reduction of sweat nitrate. NO synthesis is regulated by NOS activation (eNOS and nNOS) or synthesis (iNOS) and by substrate availability. Elevated arginase concentrations in psoriatic skin suggest that substrate competition may affect NO production. The balance of NO and reactive oxygen species is probably also important in regulating the biological actions of NO. The physiological functions of NO in the skin are being elaborated. NO release is increased following exposure to ultraviolet radiation (UVR); in eNOS null mice, dermal and epidermal apoptosis following UVR exposure is increased. Experiments in which keratinocytes and melanocytes were cocultured show melanogenesis being dependent on keratinocyte-generated NO, and UVR-induced guinea pig pigmentation is delayed following application of a NOS antagonist to the skin. Wound healing is delayed in eNOS and iNOS null mice.