Data from 988 pigs from 119 litters farrowed in two seasons of a three-breed diallel crossbreeding experiment were analyzed to estimate general combining abilities of breeds and heterosis for humoral immune response to pseudorabies virus and atrophic rhinitis vaccines. Twenty purebred boars and 85 sows of the Duroc, Landrace and Yorkshire breeds were mated to provide the nine breed-of-sire and breed-of-dam combinations. Immune response was measured after vaccination. A modified-live pseudorabies virus (PR) vaccine was administered to piglets at 28 d of age and response measured as log₂ serum neutralization titers at 56 d. An inactivated B. bronchiseptica bacterin was administered at 28, 42 and 112 d. Antibody levels were measured relative to positive and negative controls at 28, 56 and 119 d by using an enzyme-linked immunosorbent assay. The results of this study showed that ranking by breed of sire and breed of dam did not differ for general combining ability, and no evidence of significant heterosis for any immune responses was observed. Higher immune response at 56 d to B. bronchiseptica vaccine was associated with lower weaning weight (r = −.09, P<.01). Correlations of days to 100 kg with 56-d and 119-d B. bronchiseptica antibody levels were .15 (P<.01) and .12 (P<.01). The relationship between humoral immune response to PR vaccine and growth traits was similar to that observed for B. bronchiseptica vaccine. Immune response to both antigens was not associated with backfat thickness. Further research using more specifically defined antigens and homogeneous populations of animals is needed to examine nonadditive gene action on the humoral immune response in swine.