We compared fetal glucose- and arginine-stimulated insulin secretion (delta I, pM) among four groups of pregnant sheep after 10-11 days of different maternal glycemic patterns: 1) control, euglycemic; 2) low-level basal plus "pulsatile" hyperglycemic (PHG group); 3) markedly hyperglycemic (HG) group); 4) markedly hypoglycemic (LG group). Mean delta I during a hyperglycemic clamp was greatest in the PHG group (190 +/- 28 pM, P < 0.01) and least in the HG (64 +/- 13 pM, P < 0.05) and LG groups (68 +/- 15 pM, P < 0.05) compared with the control group (126 +/- 18 pM). After an arginine bolus, insulin concentration was greater in the PHG group at two of four sampling times over 30 min compared with the control group and at all times compared with the HG and LG groups. The trend in mean delta I over the postarginine sampling period (PHG 1,092 +/- 114 pM; control 921 +/- 86 pM; HG897 +/- 117 pM; LG831 +/- 57 pM) was in the same direction as for glucose and was significant (P < 0.05). Thus glucose-stimulated fetal insulin secretion is regulated by the duration and pattern, as well as the magnitude, of maternal and fetal hyperglycemia; this regulation may also extend to insulin-secretion capacity.