We conducted a prospective study of the associations between several biologic and surgical breast factors and the onset of lactation in 319 healthy, motivated, primiparous women who were breastfeeding term, healthy, appropriate for gestational age or large for gestational age infants. During the last trimester of pregnancy subjects' breasts were examined for surgical incisions, size, symmetry, and nipple protuberance, and women estimated their prenatal breast enlargement. At two visits in the first two weeks postpartum, infants were weighted naked, and mothers reported the magnitude of postpartum breast engorgement when their milk came in. Breastfeeding was evaluated at each visit, and interventions were recommended for problems, with emphasis on maximizing milk yield. Lactation was deemed sufficient when an exclusively breastfed infant achieved an average weight gain of 28.5 g or more per day between the two visits. Infants gaining less than 28.5 g per day with breast milk exclusively, and those requiring formula supplement returned for a third visit at or before 21 days of age, when final lactation outcome was assessed based on weight gain between the second and third visits. Within three weeks postpartum 85 percent of the mothers achieved sufficient lactation, whereas 15 percent had persistent milk insufficiency despite intensive intervention. Of the study population, 6.9 percent had undergone previous breast surgery. Women with periareolar breast incisions were nearly 5 times more likely to have lactation insufficiency than were those without surgery (relative risk [RR] = 4.55; 95 percent confidence interval [CI] = 2.21-9.43; P less than 0.001). Insufficient lactation was significantly associated with minimal prenatal breast enlargement (P less than 0.02) and minimal postpartum breast engorgement when milk came in (P less than 0.001). Although not statistically significant, women with inverted nipples were more likely to have lactation insufficiency compared with those with normal nipples (RR = 2.94; 95% CI 1.05-8.20; P = .07). The findings from this study indicate that certain biologic and surgical breast variables are associated with lactation insufficiency.