One hundred and seventy five Vietnamese adults with severe and complicated malaria admitted to a rural district hospital were entered into an open randomized comparative study to compare 4 treatment regimens based on artemisinin and its derivatives. The median time of defervescence was 48 h (95% confident interval [CI] 38-58 h) in those given intramuscular (i.m.) artemether, 42 h (95% CI 36-48 h) in those given artemisinin suppositories, 36 h (95% CI 30-42 h) in those receiving artesunate (i.m.) and 30 h (95% CI 18-42 h) in those receiving intravenous artesunate (P = 0.13). The respective median parasite clearance times were 30 h (95% CI 26-34 h), 30 h (95% CI 24-36 h), 24 h (95% CI 15-33 h), and 24 h (95% CI 15-33 h) (P = 0.30); the median times for recovery of consciousness were 47 h (95% CI 31-63 h), 24 h (95% CI 18-30 h), 30 h (95% CI 18-42 h), and 24 h (95% CI 4-44 h) (P = 0.18); and the mortality rates were 11.1%, 17.6%, 10.2% and 16.6%, respectively (P = 0.64). There was no significant difference in efficacy between the 4 treatments.