Experimental evidences showing the immunomodulatory effects of probiotic microorganisms have been provided by studies on immunologically intact animals. Here we compared the immunomodulation capacity of a probiotic strain of Lactobacillus plantarum on intact and cyclophosphamide-treated BALB/c mice. Although this strain fulfilled the in vitro criteria for the selection of potentially probiotic bacteria (resistance to low pH and bile, adhesion to epithelial cells and antimicrobial activity), it was unable to establish a persistent colonization in the gastrointestinal tract after intragastric gavage. The administration of L. plantarum did not modify the cyclophosphamide-induced leukopenia, but partially restored the proliferation of spleen cells from cyclophosphamide-treated mice in response to lipopolysaccharide. Our findings show that probiotic bacteria may exert immunomodulatory effects despite a limited colonization ability and may improve the immune function damaged by immunosuppressive agents.