We investigated the cellular mechanisms responsible for the inability of 8-month-old previously malnourished (PM) females to adapt their beta-cell mass during pregnancy. The evolution during pregnancy of beta-cell fraction, size and proliferation was studied. At day 21 of pregnancy beta-cell fraction increased less in PM than in control females, compared with their non-pregnant values. A slight beta-cell hypertrophy was observed during pregnancy in both groups. In control females, beta-cell 5-bromo-2'-deoxyuridine (BrdU) labelling index (LI) increased from 0.07+/-0.04% before pregnancy to 1.13+/-0.20% at day 12 and decreased thereafter to reach again basal levels at day 21. In PM females, beta-cell proliferation rate was decreased at day 12 (0.74+/-0.15%, P<0.05) but similar to controls at all other stages studied. Separate analysis of the head and tail parts of the pancreas in control animals revealed that the beta-cell fraction during pregnancy increased more in the head than in the tail; similarly, BrdU LI increased 20-fold in the head and 10-fold in the tail, compared with non-pregnant values. In PM females, no adaptation of beta-cell fraction could be observed in the head, where BrdU LI was decreased by half at day 12 of pregnancy. In PM females the lactogenic activity was twice that of controls at day 12 whereas all beta-cells expressed the prolactin receptor. In conclusion, perinatal malnutrition impairs subsequent adaptation to pregnancy by decreasing beta-cell proliferation in the head of the pancreas at a critical time during pregnancy.