Objective: To explore the effect of human immunodeficiency virus (HIV) infection and drug use on birth weight, length, and gestational duration at delivery. Methods: Subjects had a history of injection drug use or a sexual partner who was an injection drug user, were Scottish, and their HIV serostatus during pregnancy was known. Control pregnancies were matched for age, parity, ethnic group, year of delivery, and postal code sector of home address. In addition, some were matched for smoking and housing deprivation score. Birth weights were standardized for gestational age by expressing them as z scores with a mean of zero and a standard deviation of unity. Statistical analysis was by univariate and multiple regression with multilevel modeling. Results: Regression analysis for birth weight, gestational age, and gestation-adjusted birth weights (z score) included 789 pregnancies in 693 women. Human immunodeficiency virus seropositivity was associated with a z score that was 0.27 lower (P = .03), but there was no significant difference in gestational duration at delivery. Current oral or injection drug use were associated with a reduction in standardized birth weight (z score −0.27, P = .06, and z score −0.28, P = .04, respectively), and injection drug use with a reduction in occipitofrontal circumference only (1.8 cm reduction, P = .05). Injection drug use, but not the other factors, had an effect on gestational age at delivery (1.54 weeks earlier, P < .001). Conclusion: Although HIV seropositivity is associated with a small reduction in standardized birth weight, this effect is less than that attributable to smoking and may not be of clinical significance. The effect seems to be associated with placental size. Opiate use, regardless of route, had a small association with reduced birth weight, suggesting a specific drug effect. However, only injection drug use had a strong association with early delivery, and this effect was likely to be clinically significant at the population level.