It was recently reported that caffeine may reduce the clinical symptoms of asthma and may prevent the clinical manifestations of this disease. The effect of caffeine on histamine responsiveness is unknown. The effect of caffeine (5 mg/kg) and placebo on histamine responsiveness (the provocation concentration causing a 20% fall in FEV1, PC20) was studied in 10 subjects with mild asthma (prechallenge FEV1 84% of predicted value). The PC20 for histamine bronchoprovocation after caffeine ingestion was 2.65 (95% confidence limits 0.99, 7.10) mg/ml. After placebo the PC20 was 1.89 (0.96, 3.71) mg/ml. It is concluded that caffeine in a dose equivalent to about three cups of coffee has a very small effect, if any, on histamine bronchoprovocation in those with mild asthma. Specific instructions about not having drinks containing caffeine before histamine challenge are therefore not necessary.