This study examined differences in adrenocortical function between low- and high-birth-weight female neonatal pigs. Pigs born to unilaterally hysterectomized, ovariectomized sows were grouped by birth weight; "small" were < or = 1.2 kg and "large" were > 1.2 kg. Pigs were cross-fostered such that each sow had six to eight pigs that were either small or large. At 3 or 7 d of age a blood sample was obtained by venipuncture, pigs were killed, and adrenocortical cells were isolated. Adrenal weights (milligrams/kilogram BW) in small pigs were 46% greater (P = .001) than those in large pigs at both ages. Compared with those in large pigs, plasma cortisol concentrations were 70% greater (P = .006) in small pigs at 3 d and 199% greater at 7 d of age. Sensitivity of adrenocortical cell response to ACTH was enhanced at both ages in small pigs (P = .001). Corticosteroid binding globulin (CBG) binding capacity in small pigs was 75% greater (P = .03) than that in large pigs at 3 d and 26% greater at 7 d of age. Significant negative correlations existed between birth weight and relative adrenal weight, plasma cortisol, slopes of in vitro adrenocortical cell response curves to ACTH, and CBG binding capacity, irrespective of birth weight group classification. Such data indicate an association between adrenal function during early neonatal life and birth weight in female pigs. The current study does not indicate whether increased adrenal function causes or merely reflects conditions associated with low birth weight. However, we hypothesize that increased adrenal function is initiated prenatally and causes some instances of low birth weight.