Meriones unguiculatus commonly known as gerbils are widely used as animal models for a variety of parasitic infections such as Brugia malayi, Entamoeba histolytica, Giardia duodenalis, Toxoplasma gondi, Helicobacter pylori, Strongyloides stercoralis and Echinococcus multilocularis. Groups of BALB/c mice, gerbils and XID mice were studied for antibody responses to T-independent antigens. Gerbils were found to be significantly deficient in eliciting antibodies to both dextran and phosphorylcholine (PC) in comparison to BALB/c mice. The antibody response of gerbils to T-independent antigens was found to be similar to the response observed in Bruton's tyrosine kinase (Btk) deficient XID mice, which are known to be poor responders to T-independent antigens. Similar to XID mice, normal gerbil sera were found to be deficient in naturally occurring antibodies to single stranded DNA (SS-DNA), lipopolysaccharide (LPS) and phospholipids. This raises the possibility of a deficiency of CD5+ B-lymphocytes (also known as B-1 cells) in gerbils, since deficiency of this sub-population of B-lymphocytes has been attributed to the absence of such naturally occurring antibodies in XID mice. These results indicate the need to study immunogenicity of parasite T-independent antigens and their relationship to protective immunity in parasitic infections in gerbils.