Alterations of the cell-mediated and humoral immune parameters were revealed in the bivalves Modiolus kurilensis from the Sea of Japan after injection with heat-inactivated Staphylococcus aureus. Preliminary screening of the in vitro phagocytic activity (PA) and hemagglutination (HA) enabled to obtain homogeneous groups of individuals for all of the parameters to be measured. Changes in hemolymph parameters were studied over a 14-day period. High values for hemolytic activity (HL) and protein concentration (PC) persisted until 36 h, with high levels of HA persisting until 168 h. The in vitro PA level was low from 3 to 6 h postchallenge, which was caused active in vivo hemocyte elimination of the injected antigen in the first 12 h. A significant increase in the in vitro PA up to 36 h was related to a rise in the circulating total hemocyte concentration (from 6 to 12 h) and to in vivo S. aureus clearance (in the first 48 h). For the first time, a complex correlation analysis of the interplay between the cellular and humoral parameters against bacterial challenge in a bivalve revealed significant inverse correlations of PA with HL and HA during the period of these active immune responses from 3 to 48 h. The investigated immune parameters can serve as effective methods for estimation of the physiological state of the bivalve in natural and aquacultural populations under normal environmental conditions and significantly alterations under conditions of stress.