This study assessed the efficacy of rosuvastatin for reducing plasma low-density lipoprotein (LDL) cholesterol after 18 weeks of open-label, forced titration in patients with homozygous familial hypercholesterolaemia (hoFH) and compared the efficacy of rosuvastatin 80 mg and atorvastatin 80 mg. Forty-four patients aged 8-63 years (body mass >or=32 kg) entered the study; 4 had portacaval shunts and 11 were receiving plasmapheresis. Patients sequentially received rosuvastatin 20, 40 and 80 mg/day for 6 weeks. Patients remaining in the trial after 18 weeks received double-blind, randomised crossover treatment with rosuvastatin 80 mg/day and atorvastatin 80 mg/day for 6 weeks each. After 18 weeks, mean (S.D.)% reduction from baseline in LDL cholesterol was 22 (21)% overall and by 26 (15)% in 29 patients who neither had a portacaval shunt nor were receiving plasmapheresis. Seventy-two percent of the patients had >or=15% reductions in LDL cholesterol and were considered responders and included patients who had portacaval shunts or were receiving plasmapheresis. Mean LDL reductions from baseline after crossover treatment (n=21) with rosuvastatin 80 mg and atorvastatin 80 mg were 19 and 18%, respectively. All treatments were well tolerated. Rosuvastatin may have therapeutic value in the management of hoFH.