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A sensitive and selective gas chromatographic method is described for determining the diuretic and antihypertensive drug chlorthalidone in plasma, urine and erythrocytes. Use is made of an alkali flame ionization detector (nitrogen detector), and the chlorthalidone and internal standard are chromatographed as methyl derivatives. Down to 10 ng of drugs in the biological sample can be measured accurately, with a standard deviation of 5%. Because the concentration of chlorthalidone found in erythrocytes is 50-100 times higher than that in plasma, the influence of haemolysis on the plasma concentration has been investigated. In addition, a pharmacokinetic study with human volunteers revealed that the apparent concentration of the drug found in plasma can be much too low (by more than 50%), if the plasma is not separated from the erythrocytes immediately after venipuncture. Precautions to be observed to ensure correct handling of blood samples (so that results for plasma concentrations will be reliable) are stressed. The findings have application in kinetic studies on chlorthalidone.