1. Uptake of glucose by the rat diaphragm in vitro and utilization of glucose by human erythrocytes were inhibited by urea, creatinine and, to an even greater extent, by urea plus creatinine. Guanidine, methylguanidine and guanidinoacetic acid individually had a small enhancing effect on glucose uptake and utilization but collectively there may be an additive effect. Urate, p-cresol and p-cresylsulphate had no appreciable effects.
2. Dialysis of uraemic patients greatly decreased, or abolished, the inhibitory effect of their sera on glucose uptake by hemidiaphragms.
3. Administration of urea or creatinine lowered the oral glucose tolerance of patients with moderately impaired renal function.
4. In ten normal dogs intravenous glucose tolerance curves were unchanged during methylguanidine administration, whereas in five dogs oral glucose tolerance curves became flattened.
5. Fasting blood glucose of five alloxan-diabetic dogs was decreased during administration of methylguanidine and increased again when administration was discontinued.