No therapy has been proved to be effective for patients with severe chloroquine poisoning, which is usually fatal. In a retrospective study of 51 cases, we found that ingestion of more than 5 g of chloroquine was an accurate predictor of a fatal outcome, and therefore chose this dose as the criterion for severe chloroquine poisoning. We selected as a control group 11 consecutive patients who had ingested more than 5 g of chloroquine between July 1983 and December 1985. We then undertook a prospective study to determine whether a better outcome could be obtained with immediate mechanical ventilation and the administration of diazepam and epinephrine. Eleven consecutive patients who ingested more than 5 g of chloroquine in 1986 received this combination therapy. Ten of these patients survived, whereas only one control had survived (P = 0.0003). There was no significant difference between the combination-therapy and control groups in age (29 +/- 3 vs. 27 +/- 2 years), amount of chloroquine ingested (7.5 +/- 0.5 vs. 8.5 +/- 0.8 g), systolic arterial pressure (74 +/- 2 vs. 74 +/- 3 mm Hg), or QRS duration (0.14 +/- 0.01 vs. 0.14 +/- 0.01 second). In our combination-therapy group, blood chloroquine levels ranged from 40 to 80 mumol per liter, whereas a literature search showed that no patient in whom blood levels were more than 25 mumol per liter had survived. These preliminary data suggest that combining early mechanical ventilation with the administration of diazepam and epinephrine may be effective in the treatment of severe chloroquine poisoning.