A continuing survey of the genetic variability of different mouse strains to acetazolamide teratogenesis demonstrated the WB/ReJ strain expresses a high frequency of induced subcutaneous edema in day 15 fetuses. In treated WB/ReJ fetuses, the probability of expression of edema is independent of the expression of forelimb ectrodactyly and, with the dosage regime, there is no significant increase in acetazolamide-induced resorption. It was surprising to find a high frequency of spontaneous edema on day 15 in untreated WB/ReJ fetuses. The spontaneous edema is a transient trait with maximum expression (56%) on day 14, and it is resolved by day 17 without apparent consequence to the survival of previously affected fetuses. There is no sex dimorphism in the liability to express the transient edema. Preliminary genetic crosses to investigate the spontaneous edema were made between WB/ReJ and the C57BL/6J strain, which historically had not be observed to express spontaneous edema. A low frequency of spontaneous edema was observed on day 14 in both C57BL/6J and the reciprocal F1 fetuses. The trait is not additive because there is dominance deviation of the BC1 fetuses in the direction of the F1 fetuses. The data were fitted to a threshold model suggesting that the developmental liability to express the difference in transient edema is determined by more than one gene, but the data can be interpreted by a minimum of two loci with duplicate epistasis. The observed differences in frequencies of edema suggest the genetic model can be tested with relatively few test crosses.