High-dose chloroquine therapy for porphyria cutanea tarda is rarely used now because of its hepatic side-effects. The mechanisms of the effects and side-effects are poorly understood. We describe here effects, side-effects and long-term follow-up in 57 patients with a first-time diagnosis of porphyria cutanea tarda treated with 1-3 phlebotomies followed by 250 mg chloroquine phosphate daily for 7 days. A hepatotoxic reaction with high serum aminotransferases occurred in almost all patients. Within 3 months, clinical remission was obtained in all patients, and biochemical remission in almost all patients. Relapse occurred in 27 patients after 0.5-12 years. Subjective side-effects occurred more frequently in women, who also had higher maximum ALAT, ferritin and uroporphyrin values during treatment. Both subjective side-effects and ALAT during treatment correlated with pre-treatment uroporphyrin excretion and maximum uroporphyrin during treatment, but not with markers of hereditary haemochromatosis.