Carrying the cytosine-adenosine (CA)19 repeat polymorphism in insulin-like growth factor-1 (IGF1) is associated with lower serum proteins and decreased prostate cancer risk. Carrying the -202A/C genotype in insulin-like growth factor binding protein-3 (IGFBP3) also has been associated with lower serum levels of the binding protein. However, the association between this variant and prostate cancer is inconsistent. To test the hypothesis that inconsistencies are partly due to cancer grade-specific differences in strength and direction of associations, we reanalyzed data from our previous Durham Veterans Administration Hospital study of blacks and whites comprising 47 cases (19 African Americans) with Gleason sum ≥7, 50 cases (30 African Americans) with Gleason sum <7 and 93 controls (49 African Americans). Compared to controls, the association between carrying the IGFBP3 C allele and prostate cancer risk was in ORLow-Gleason=4.0; 95% CI: 1.4-12.3 compared to ORHigh-Glaeason=1.0; 95% CI: 0.4-2.2. Association patterns were similar in African Americans (ORLow-Gleason=3.6; 95% CI: 1.0-13.2 vs. ORHigh-Gleason=1.4; 95% CI: 0.4-2.3) and whites (OR LowGleason=5.6; 95% CI: 0.6-49.0 vs. ORHigh-Gleason=0.6; 95% CI: 0.2-2.2). The inverse association between carrying the IGF1 (CA) 19 repeat variant did not vary by grade or ethnicity. If confirmed in larger studies, these findings support the hypothesis that the association between IGFBP3 C allele and prostate cancer is grade specific in both ethnic groups.