Measurement of transcutaneous oxygen pressure (TCPO2) is an established and noninvasive way of assessing cutaneous hypoxia. Since the degree of oxygenation modulates fibroblast growth and synthesis, we investigated the presence of cutaneous hypoxia in patients with systemic sclerosis (SS). We measured TCPO2 of the involved skin of the dorsal aspect of the forearm in 33 patients with SS and 16 control individuals (normal subjects and patients with Raynaud's disease). The degree of forearm skin thickness was assessed clinically as mild, moderate, or severe. The TCPO2 measurements were obtained at a sensor temperature of 44 degrees C, which causes maximal vasodilation and eliminates the variables associated with vascular tone. Measurements were recorded while patients were breathing room air or 31% oxygen delivered by a Ventimask system (Baxter Healthcare, Ocala, Fla). We also measured the TCPO2 of the medial aspect of the arm when this site was uninvolved. We found that sclerodermatous skin is hypoxic when compared with the uninvolved skin of patients with SS or control individuals. The TCPO2 values were indirectly related to skin thickness; thus, patients whose skin was severely thickened had the lowest TCPO2 values. There was no correlation of TCPO2 values with pulmonary function tests or arterial oxygen pressure. The TCPO2 levels of patients with Raynaud's disease did not differ from other control individuals. The administration of oxygen increased TCPO2 readings in patients with SS to normal values. We conclude that the thickened skin of patients with SS is hypoxic and suggest that TCPO2 measurements may be helpful in objectively assessing the degree of skin thickness. The hypoxia demonstrated in SS skin may play a role in the modulation of dermal fibroblast proliferation and synthetic activity.