The in vivo and in vitro effects of a hypoglycaemic fragment of human growth hormone containing the sequence H2N-Ile-Pro-Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala-Met-Leu-COOH (hGH 4-15) on 2-deoxy-[1-14C]-D-glucose uptake in adipocytes were studied. The isolated cells from rats after a single intravenous injection of hGH 4-15 (1 mg/kg) significantly increased uptake of 2-deoxyglucose (p less than 0.005). Adipocytes from untreated rats pre-incubated with the hGH fragment (10 micrograms/ml) at 37 degrees C for 30 min also clearly showed an elevated uptake of 2-deoxyglucose in the absence and the presence of exogenous insulin. The effect of hGH 4-15 was concentration-dependent, steadily increasing with the maximum effect at 10 micrograms/ml. The present findings suggest that the enhancement of glucose transport in target tissues may be a major contributing factor to the hypoglycaemic action of the amino-terminal fragments of human growth hormone.