AbstractAlthough natural mumps virus infection is believed to induce lifelong immunity, our laboratory was confronted with 82 patients who developed mumps‐evoking lesions but exhibited serological evidence of a booster immune response, namely a rise or a high titer of virus‐specific IgG, without IgM. In order to provide arguments favoring the existence of recurrent mumps attacks, the age, symptomatology, and humoral response of these patients (group 1) were compared to that of 82 randomly selected true primary infected patients (group 2), 10 parainfluenza virus‐infected patients (group 3), and 20 noninfected mumps‐immune subjects (group 4), Enzyme‐linked immunosorbent assay (ELISA) procedures with different viral antigenic preparations were used for determination of specific IgM, IgA, IgG, IgG subclasses, and IgG avidity. The patients of group 1, older than those of group 2 (28 vs. 10 years, P <0.0001), presented a significantly less severe and less typical symptomatology. Against the whole virus they exhibited IgG of higher avidity (P < 0.001), a lower prevalence and titer of IgA (10 vs. 68%, P < 0.0001 and 278 vs. 5,009, P < 0.001, respectively). Values obtained for IgG 1, 2, and 3 were significantly different between the two groups. Prevalence and absorbance of nucleocapsid‐directed IgG 3 were significantly lower in group 1 (27 vs. 46%, P < 0.01 and 0.444 vs. 0.869, P < 0.01, respectively). A significant discrepancy also allowed patients from group 1 to be distinguished from those of groups 3 and 4. So the presumed mumps‐reinfected patients were different from primary infected ones and presented features reminiscent of a secondary immune response, suggesting the not uncommon occurrence of symptomatic reinfections by the mumps virus. This concept is of importance in medical practice. © 1995 Wiley‐Liss, Inc.