Insulin resistance syndrome (IRS)-related phenotypes, such as hyperinsulinemia, obesity-related traits, impaired glucose tolerance, dyslipidemia, and hypertension, tend to cluster into factors. We attempted to identify loci influencing the factors of IRS-related phenotypes using phenotypic data from 261 nondiabetic subjects distributed across 27 low-income Mexican-American extended families. Principal component factor analyses were performed using eight IRS-related phenotypes: fasting glucose (FG), fasting specific insulin (FSI), BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), HDL cholesterol, ln triglycerides (ln TGs), and leptin (LEP). The factor analysis yielded three factors: factor 1 (BMI, LEP, and FSI), factor 2 (DBP and SBP), and factor 3 (HDL and ln TG). We conducted multipoint variance components linkage analyses on these factors with the program SOLAR using a 10--15 cM map. We found significant evidence for linkage of factor 1 to two regions on chromosome 6 near markers D6S403 (logarithm of odds [LOD] = 4.2) and D6S264 (LOD = 4.9). We also found strong evidence for linkage of factor 3 to a genetic location on chromosome 7 between markers D7S479 and D7S471 (LOD = 3.2). In conclusion, we found substantial evidence for susceptibility loci on chromosomes 6 and 7 that appear to influence the factors representing the IRS-related phenotypes in Mexican-Americans.