The effect of a 7-day course of intravenous penicillin (6 million units/day) on severe, advanced leptospirosis was examined in a randomised, placebo-controlled, double-blind trial involving 42 patients. Every measurable aspect of the disease was favourably affected by penicillin. Fever lasted more than twice as long in the placebo group (11.6 [SD 8.34] days vs 4.7 [4.19] days, p less than 0.005), and by the fourth day after starting penicillin more than half the treatment group, but only 1 of 19 in the placebo group, were afebrile (p less than 0.005). Creatinine rises persisted more than thrice as long in the patients receiving only placebo (8.3 [8.46] days vs 2.7 [1.90] days; p less than 0.01). Penicillin also shortened the hospital stay and prevented leptospiruria. Intravenous penicillin should be given to patients with severe leptospirosis, even if therapy can be begun only late in the course of their disease.