Abstract The importance of genetic and environmental variation in condition in shaping evolutionary trade-offs have recently been subject to much theoretical discussion, but is very difficult to investigate empirically in most field-based systems. We present the results from mechanistic experimental manipulations of reproductive investment and condition in two female colour morphs (‘orange’ and ‘yellow’) of side-blotched lizards (Uta stansburiana). We investigated the interactions between throat colour morphs, condition, local social environment and female survival using path-analysis. Using follice-ablation experiments, we show that large clutch size has a negative effect on field survival among yellow females, and that this effect is partly mediated by immunosuppressive effects of large clutches. In orange females these effects were less pronounced, and there was a negative survival effect of strong antibody responses. Hence, we experimentally confirmed our previous findings of correlational selection between female morphotype and immunocompetence, an important condition trait. Manipulation of corticosterone revealed multiple (‘pleiotropic’) direct and indirect effects of this hormone on both condition and reproductive traits. We argue that interaction effects (e.g. between local environments and genotypes) could explain a substantial fraction of variation in condition and reproduction in natural populations. Increased attention to such interaction effects and their fitness consequences will provide novel insights in field studies of selection and reproductive allocation.