Summary1. Frusemide produced hyperglycaemia in mice when administered together with diazoxide. The interaction between the drugs in elevating the blood sugar was shown to be additive. 2. The diuretic, natriuretic and kaliuretic effects of frusemide were very markedly attenuated by diazoxide. 3. Neither ethacrynic acid nor hydrochlorothiazide exerted any effect upon blood sugar when administered together with diazoxide. 4. Bilateral nephrectomy completely prevented the hyperglycaemic effect of frusemide in normal mice and in mice treated with diazoxide. Diazoxide itself still produced hyperglycaemia in nephrectomized mice. 5. Frusemide, ethacrynic acid and diazoxide, but not hydrochlorothiazide, each produced hyperglycaemia in alloxan-diabetic mice, this being prevented by bilateral nephrectomy.