Approximately 80% of all human conceptions are lost prior to term, and about 6% of all human newborns exhibit in-utero fetal growth retardation resulting in perinatal mortality and a major share of perinatal morbidity. Recent interest has focused on the plausibility of an MHC-linked immunological effect in cases of spontaneous abortions in which no possible cause, particularly a chromosome abnormality, is indicated. Paradoxically, placenta has been shown to serve as an efficient immunosorbent where antipaternal MHC antibodies on binding to target MHC antigen-bearing placenta are internalized and rapidly degraded, thereby preventing potential damage to the fetus. We, in our attempts to resolve if active immune responses on the part of female following early recognitive events during pregnancy play any decisive role in the reproductive process, raised a highly inbred colony of mice (Balb/cJ, Jackson Labs, USA) to produce H-Y antibodies. An outbred colony of mice (Swiss, AIIMS) was maintained to study the cumulated effect of H-Y and H-2 antibodies on the sex ratio, reproductive performance, litter size, and fetal wastage. A definite sex ratio was observed in control groups. However, the H-Y antibodies produced by hyperimmunized inbred female mice before fertilization, significantly (P less than 0.01) reduced the sex ratio. The combined effect of H-Y and H-2 antibodies on the pregnant outbred mice produced more lethal congenital abnormalities. There was a significant (P less than or equal to 0.01) loss in the reproductive performance of male mice born from hyperimmunized female mice both inbred and outbred colonies.(ABSTRACT TRUNCATED AT 250 WORDS)