Identification of modifiable risk factors which contribute to tumour metastasis is an important goal of cancer prevention research. This study was designed to evaluate the role of moderate exercise conditioning on the in vivo retention of radiolabelled H-ras-transformed fibroblasts (CIRAS 1 and CIRAS 3 cell lines) in mice with (C3H/He-bg2J/+) and without (C3H/HeJ) the beige (bg) mutation which produces impaired natural killer (NK) cell function. Mice were randomly assigned to treadmill training (20 m/min, 30 min/day, 5 times/week) or remained sedentary for 9 weeks. C3H beige mice had significantly higher retention in the lungs of CIRAS 1 tumour cells (P < 0.0001) than genotypically normal C3H/HeJ mice. There was a significant main effect of exercise conditioning (P < 0.05) with trained mice (irrespective of genotype) having lower tumour retention (44 +/- 3%) than sedentary controls (53 +/- 3%). Comparing the in vivo retention of CIRAS 1 and CIRAS 3 in the lungs of genotypically normal mice, we observed higher retention of CIRAS 1 (48 +/- 2%, compared with 18 +/- 2% for CIRAS 3; P < 0.0001). There was a significant interaction effect of exercise and tumour type (P < 0.05); trained mice had a lower retention for CIRAS 1 than sedentary controls (43 +/- 3%, compared with 53 +/- 3%), while training status had no effect on CIRAS 3 retention. There were no significant differences in final tumour multiplicity in the lung as a function of exercise condition. The data suggest that exercise conditioning reduces some measures of in vivo burden but only for the less aggressive tumour variant (CIRAS 1); further, innate immune mechanisms other than NK cells are likely to be involved in this modest protective effect.