Women differ markedly from men in their metabolic response to caloric deprivation. To determine if these differences could be attributed solely to changes in insulin concentration, a group of 8 women was matched with a group of 7 men so that the mean fall in serum insulin during a 72-h fast did not differ between the groups. Glucose levels fell to a greater degree in the women than in the men. The serum concentrations of free fatty acids and ketone bodies rose more rapidly in the women and closely paralleled the earlier rise in glucagon concentrations. Over the first 36 h of fasting the change in free fatty acids was positively correlated to the change in glucagon and negatively correlated to the change in insulin. For the second 36 h of fasting, only changes in glucagon correlated with changes in free fatty acids. These correlations were true for both sexes and support the hypothesis that glucagon plays a physiologically significant role the regulation of lipolysis during starvation.