Both in vivo macrophage activation and in vitro monocyte activation were compared using chickens homozygous for each of two biochemically and serologically similar B-complex recombinant (B(F2-G23)) haplotypes. Chickens carrying the parental (non-recombinant) B haplotypes (B2 and B23) were included for relative comparison, although the genetic backgrounds for these strains were different from the background of the recombinants. Elicited peritoneal macrophages from R4/R4 (international designation B(2r3)) chickens expressed levels of sheep erythrocyte phagocytosis which were significantly higher (P< 0.05) than those from R2/R2 (B(2rl)) chickens. Differences between chickens with B genotypes were analogous to the differences demonstrated previously between B2/B2 and B23/B23 chickens. Similarly, lipopolysaccharide (LPS)-activated monocytes from R4/R4 chickens also expressed significantly higher (P< 0.05) levels of phagocytosis when compared with R2/R2 and B23/B23. In both cases, the functional level of macrophages from R2/R2 chickens was similar to that of B23/B23 cells, whereas macrophages from R4/R4 chickens were similar in functional capacity to those from B2/B2 chickens. These results suggest that R2 and R4 recombinants, despite their demonstrated similarities, may differ in DNA regions which include genetic factors controlling macrophage responsiveness.