The health of 155 former workers in a US military research program who had received multiple vaccines and 265 matched community controls was assessed. The study population was mostly male (83%) and elderly (median age, 69 years). Multiply immunized (MIP) subjects received vaccines and/or skin tests (median = 154) over a median of 17.3 years; interval from start of immunizations to survey completion was 15-55 years (mean = 43.1 years). MIP subjects characterized themselves as slightly less healthy than controls (P = 0.057). Fatigue (but no other symptom) was reported more frequently in the MIP group (P = 0.011), but was not associated with number of injections, number of vaccines, or time in program. No differences between MIP and control groups were seen for numerous self-reported medical conditions. Several statistically significant abnormalities were seen in clinical laboratory tests among MIP subjects, but none appeared to be clinically significant. A significant difference in frequency of monoclonal spikes and/or paraprotein peaks between MIP (12.5%) and control (4.5%) groups (RR = 2.7, P < 0.003) was observed; no associations with lifestyle, vaccine exposure, or medical conditions were found.