To characterize the four common Qa-1 allelic products, we examined in detail the CTL-defined determinants encoded by Qa-1. In previous studies with anti-Qa-1 CTL and alloantisera, investigators have described antigenic determinants present on Qa-1(a) and Qa-1(b) antigens, but they have defined Qa-1(c) and Qa-1(d) exclusively by their cross-reactivity with Qa-1(a) and/or Qa-1(b) determinants. To delineate further the CTL-defined determinants encoded by Qa-1(d), we generated CTL clones with Qa-1(d) specificity and demonstrated that the Qa-1(d) molecule expressed determinants that were not detected on Qa-1(a), Qa-1(b), or Qa-1(c) target cells. Other CTL clones derived from anti-Qa-1(d) MLC recognized new antigenic determinants on Qa-1(c) that cross-reacted with Qa-1(d). Each of the four common Qa-1 phenotypes was shown to exhibit unique antigenic determinants. In addition, Qa-1(d) and Qa-1(a) and Qa-1(d) anti-Qa-1(b) CTL confirmed extensive cross-reactivity among these Qa-1 alloantigens. Analysis of CTL from these four immunizations also resulted in the isolation of Qa-1(a)-specific and Qa-1(d)-specific CTL clones that cross-reacted with H-2D(f) and H-2K(s), respectively.