Obesity is common in women and is associated with a number of adverse health outcomes including cardiovascular disease, infectious diseases, and cancer. We explore the relationship between obesity and immune cell counts in women in a longitudinal study of 322 women from 1999 through 2003 enrolled as HIV-negative comparators in the Women's Interagency HIV Study. Body mass index (BMI, kg/m(2)) was categorized as normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), obese (BMI 30-34.9), and morbidly obese (BMI >/=35). CD4 and CD8 counts and percents and total lymphocyte and white blood cell (WBC) counts were measured annually using standardized techniques. A mixed model repeated measures analysis was performed using an autoregressive correlation matrix. At the index visit, 61% of women were African American; mean age was 35 years, and median BMI was 29 kg/m(2). Immunologic parameters were in the reference range (median CD4 count, 995 cells/mm(3); CD8 count, 488 cells/mm(3); total lymphocyte count, 206 cells/mm(3); median WBC, 6 x 10(3) cells/mm(3)). In multivariate analyses, being overweight, obese, or morbidly obese were independently associated with higher CD4, total lymphocyte, and WBC counts than being normal weight; morbid obesity was associated with a higher CD8 count. The strongest associations between body weight and immune cell counts were demonstrated in the morbidly obese. Increasing body weight is associated with higher CD4, CD8, total lymphocyte, and WBC counts in women. Investigation into the impact of obesity on immune function and long-term adverse outcomes is needed.