The S2 line of Drosophila simulans, an isofemale line from a natural population at Mishima, Japan, was found to have high crossability with D. melanogaster. Over 80% of the S2 females mated with D. melanogaster males, while only 2.4- 14.2% of control females from other D. simulans lines mated. The reciprocal mating (D. melanogaster female x S2 males) was in normal range (35-50%). The crossability of the F1 females between the S2 and other normal simulans lines was slightly higher than the control females. The high crossability is caused by at least two genes, one on the second and the other on the third chromosome which act additively.