Plasma corticosterone levels during lactation were examined in inbred A/J (A) and C57BL/6J (C)mice. Following shock, lactating A females showed a diminished corticosterone response relative to nonlactating controls on day 5 of lactation, but not on day 12. In contrast, plasma corticosterone levels of lactating C females 5 and 15 min following shock were lower than those of controls on day 12, but not on day 5. Consistent with these findings, lactating A females had significantly lower plasma levels of corticosterone 15 min following nonnociceptive treatments (involving distrubance, exposure to novelty, and pup manipulation) when tested on day 5 than they did when tested on day 12, whereas lactating C females had lower levels on day 12 than on day 5. Lactating females of each strain showed the same response to shock on day 12 if they reared A pups as they did if they reared C pups. This indicates that the difference found between the strains on day 12 was due to a difference in some property of A and C mothers, rather than to a difference in a characteristic, such as suckling patterns, of the pups of the two strains. It was also found that at long intervals following shock (45 and 90 min) 5-day lactating C females had higher levels of plasma corticosterone than did controls. There was no effect of lactation on resting adrenocorticoid levels in A or C females at either 5 or 12 days. The results indicate that laboratory mice show changes in hypothalamo-pituitary-adrenal activity during lactation which both vary with strain of the mother, and differ in several respects from those previously reported for rats.