The possibility of a circadian rhythm in the toxicity of methotrexate was investigated in rats after a single intravenous bolus. Indices of haematological, renal and hepatic toxicity were studied, as were the pharmacokinetics of the drug. All the parameters showed a circadian variation, with maximum toxicity occurring after dosage of 06.00 h and minimum toxicity after dosage at midnight. Administration at the other two time points, 12.00 h and 18.00 h, gave intermediate results.