Propylthiouracil (PTU), an antithyroid thioureylene with immunomodulatory properties, has been shown to be effective in the therapy of patients with plaque psoriasis. The mechanism of action of antithyroid thioureylenes in psoriasis remains unknown. Propylthiouracil is a commonly used agent in the treatment of patients with Graves' hyperthyroidism, a condition associated with elevated levels of interleukin-12 (IL-12), which fall significantly after propylthiouracil treatment. IL-12 is believed to play a pivotal role in the development of psoriasis. Production of IL-12 is modulated by the anti-inflammatory cytokine IL-10. The effect of PTU on IL-12 and IL-10 levels was, therefore, studied in twelve patients with plaque psoriasis. Treatment with 300 mg of PTU daily in divided doses for three months produced significant improvement of the PASI and histological scores in the patients. Serum IL-12 concentrations were undetectable at baseline and did not change with treatment. IL-10 concentrations were 1.39 +/- 1.49 pg/ml (mean +/- SD) at baseline, and showed no significant change after 2 weeks (1.63 +/- 1.61 pg/ml and 12 weeks 1.15 +/- 1.58 pg/ml of treatment with PTU. The data suggest that the clinical improvement with patients with psoriasis treated with PTU is not due to a fall in circulating IL-12 or a rise in IL-10 concentrations. Although the drug may have effects on lesional production of these cytokines this is not reflected in the circulating levels. It is speculated that the beneficial effect is likely mediated by an inhibitory effect on keratinocyte proliferation or promotion of apoptosis in these proliferated keratinocytes.