Fine and gross motor performance in 4-year-old children was examined in relation to prenatal exposure to alcohol, caffeine, tobacco, and aspirin in a longitudinal prospective population-based study. Multiple regression analyses of data from 449 children indicated statistically significant relationships between moderate levels of prenatal alcohol exposure and increased errors, increased latency, and increased total time on the Wisconsin Fine Motor Steadiness Battery and poorer balance on the Gross Motor Scale, even after adjustment for relevant covariates. Most of these alcohol-related motor findings were linear, suggesting no safe level of exposure. Alcohol scores from the period prior to pregnancy recognition were the most predictive of decrements in motor performance. Although moderate prenatal alcohol exposure was also related to lower IQ scores in this same cohort, the motor effects were independent of IQ. Some relationships with aspirin and caffeine were also found, but they were difficult to interpret.