The heat generated by cultures of a strain of Escherichia coli and of a β-lacta- mase- and a non- β-lactamase-producing strain of Staphylococcus aureus were registered by a flow microcalorimeter of the heat conduction type. When exposing the non-β-lactamase- producing strain to benzylpenicillin, an effect that appeared to correspond to the ‘paradoxical zone phenomenon’ was found, i. e. the inhibitory effect on the bacterial metabolism, as judged from the heat generated, was smaller when using 0.1-0.2µg ml-1 of benzylpenicillin (5 and 10 X minimum inhibitory concentration, MIC) than with 0.04 fig ml-1 (2XMIC) and 2.0-200 µg ml-1 (100-10,000 X MIC). Similar paradoxical response were found when the effects of ampicillin on E. coli and on the non-β-lactamase-producing strain of S. aureus were studied. In the β-Mactamase-producing strain, no decrease in the heat was obtained when benzylpenicillin was used in concentrations up to 5.0 µg ml-1 (10XMIC), whereas a drug concentration of 50 µg ml-1 (100XMIC) caused a slight reduction. The addition of dicloxacillin in concentrations of 0.25-12.5 µg ml-1 (2-100XMIC) caused a concentration-dependent reduction in the heat developed. © 1979 S. Karger AG, Basel.