Both the human immunodeficiency virus (HIV) and environmental stress have been independently associated with decreased cognitive functioning in children. Given that they are also known to have a strong relationship with each other, the present study sought to test the hypothesis that children in conditions of high environmental risk would be at greater risk for the cognitive complications related to immunosuppression. A retrospective review was conducted to examine the records of 141 children treated at a large pediatric AIDS clinic from 1993 to 2000. CD4+ lymphocyte levels were recorded from laboratory results and IQ scores were recorded from routine psychological evaluations. Key indicators of environmental risk were collected and combined into one measure of overall environmental risk. Pearson product moment correlations were conducted to examine the relationship between environmental risk, age-adjusted CD4 and IQ. Results indicated a significant correlation between CD4 and IQ, with higher levels of immunocompetence predicting higher IQ scores. When subjects were dichotomized based on their environmental risk score, there was no relationship between CD4 count and IQ in the low environmental risk group. In contrast, CD4 was positively associated with IQ in the high environmental risk group. It is proposed that this may be due to gp120 levels in immunocompromised children being particularly toxic to the hippocampus and cortex under conditions of high stress but not so under conditions of low stress.