Objective: To assess the influence of maternal HIV status and orphanhood on child mortality and physical well-being. Design: Retrospective cohort study with > 10 years of follow-up. Methods: From population-based surveys in Karonga District, Malawi in the 1980s, 197 individuals were identified as HIV-positive. These individuals and 396 HIV-negative individuals matched for age and sex, and their spouses and offspring, were sought in 1998-2000. Results: All but 11 of the index individuals were traced, identifying 2520 offspring; of these, 1106 offspring were included in analyses. Among those with HIV-positive mothers, mortality was 27% [95% confidence interval (CI), 17-38] in infants (1-30 days), 46% (95% CI, 34-58) in those under 5 years and 49% (95% CI, 38-61) in those under 10 years. The corresponding figures for those with HIV-negative mothers were 11% (95% CI, 8-13), 16% (95% CI, 13-19) and 17% (95% CI, 14-20). Death of HIV-positive mothers, but not of HIV-negative mothers or of fathers, was associated with increased child mortality. Among survivors who were still resident in the district, neither maternal HIV status nor orphanhood was associated with stunting, being wasted, or reported ill-health. Conclusions: Mortality in children under 5 years is much higher in children born to HIV-positive mothers than in those born to HIV-negative mothers. With 10% of pregnant women HIV-positive, we estimate that approximately 18% of under-5 deaths in this population are attributable to HIV. Most of the excess is attributable to vertical transmission of HIV. Our findings suggest that, in terms of physical well-being, the extended family in this society has not discriminated against surviving children whose parents have been ill or have died as a result of HIV/AIDS.