Thirty-six female pigs selected for three generations for high (HS, n = 18) and low (LS, n = 18) serum cholesterol at 56 d of age were used to test the hypothesis that the two populations would respond differently to a high-fat, high-cholesterol diet (HD) and a low-fat, low-cholesterol diet (LD). The animals were four-way crosses (Chester White x Landrace x Large White x Yorkshire). All pigs were fed a standard cornsoybean meal starter diet from weaning (at 4 wk) to 8 wk of age and a grower diet from 8 to 12 wk of age. Initial serum total cholesterol concentration at 12 wk of age was higher (P < .05) in HS than in LS pigs (94.6 vs 76.9 mg/dL, respectively). The effect of genetic background persisted throughout the 13-wk experiment (25 wk of age); there was no interaction between diet and genetic background in serum total cholesterol (final concentrations were 114.3 mg/dL in HS-HD; 107.0 mg/dL in HS-LD; 105.9 mg/dL in LS-HD; and 89.7 mg/dL LS-LD). Trends over time revealed significant effects of diet (P < .01) and genetic background (P < .01) on serum total cholesterol. There was no effect of genetic background on high-density lipoprotein-cholesterol concentration; high-density lipoprotein-cholesterol as a percentage of serum total cholesterol was similar for all groups: 43% for HS-HD, 48% for HS-LD, 42% for LS-HD, and 45% for LS-LD. Serum triglycerides, glucose, total protein, albumin, total bilirubin, inorganic P, Ca, Mg, and Cl were unaffected by diet or genetic background. Serum urea N and K were higher in HD than in LD pigs, and alkaline phosphatase (P < .03) and creatinine (P < .01) were higher in HS than in LS pigs (P < .01). Mean initial BW at age 12 wk was 35.7 kg for HS and 30.9 kg for LS pigs (P < .05), and the difference persisted throughout the experiment. The HS pigs were larger (P < .02) and had less backfat (P < .01) at the end of the experiment than the LS pigs. The data did not support the hypothesis that growing pigs selected for high serum cholesterol respond differently from those selected for low serum cholesterol to the ad libitum consumption of a high-fat, high-cholesterol diet. Instead, serum total cholesterol values in both groups, although different from each other in initial concentrations, increased linearly with time on experiment in response to a high-fat, high-cholesterol diet with no diet x genetic interaction.