Babesia gibsoni ribosomal phosphoprotein P0 (BgP0) was identified as an immunodominant cross-reactive antigen with B. microti. The BgP0 gene is a single copy with a predicted open reading frame of 942 bp and 314 amino acids. The BgP0 was expressed as a glutathione S-transferase fusion protein in Escherichia coli. The serum raised in mice with the recombinant BgP0 showed a specific band with a 34-kDa molecular mass in the extracts of B. gibsoni and B. microti merozoites. Furthermore, the intraperitoneal (i.p.) immunization of rBgP0 and Freund's adjuvant induced strong humoral response consisting of mixed immunoglobulins IgG1 and IgG2a in BALB/c mice. Following the challenge with B. microti, these mice delayed the onset of parasites and significantly reduced the peripheral parasitemia. On the other hand, passive-transfer of purified anti-BgP0 IgG into SCID mice showed partial protection against B. microti challenge infection. It was only effective in restricting the initial parasitemia but not later during its progress. Taken together, the immunological response elicited by rBgP0 protected the mice against B. microti challenge infection. These data suggest that BgP0 is a potentially universal vaccine candidate for both B. gibsoni and B. microti infections.