The objective of this study was to assess changes in the family situation of HIV-infected women who have recently given birth. As part of a prospective perinatal HIV transmission study, interviews were conducted with a subset of HIV-infected women at 18 to 24 months postpartum, and answers were compared with baseline information obtained during pregnancy. Standardized scales were used to assess levels of psychosocial functioning. A convenience sample of 129 HIV-infected women enrolled during pregnancy was interviewed at 18 to 24 months postpartum. At delivery, the women were young (median age, 22 years), primiparous (57%), and asymptomatic (93%). When baseline and follow-up data were compared, more women were living alone (1% versus 6%; p = 0.03), fewer women were living with their partners (98% versus 73%; p < 0.001), and 30% of families had reduced incomes. At follow-up, 10% of partners had died, and more partners than wives had become ill or died (21% versus 4%; p = 0.02). Most children (78%) were living with their mothers, but only 57% of the HIV-infected women were the primary caretakers. Fewer women had disclosed their HIV status to others (e.g., family, friends) than to their partners (34% versus 84%; p < 0.001), largely because of fear of disclosure. The women appeared to have high levels of depression and worry. The women's greatest worries were about their children's health and the family's future. Within 2 years after childbirth, substantial change within the families of HIV-infected women was evident. These were manifest by partner illness or death, family separation, reduced family income, shifting responsibilities for child care, and signs of depression and isolation. Providing family support is a major challenge in Thailand as the perinatal HIV epidemic progresses.