A daily random light-dark regime (RLD), in which the onset of the photophase occurred at a random time of the 24-h day, significantly shortened the life span of adult Drosophila rnelanogaster in 8 out of 23 strains tested. For the eight sensitive strains, the mean percent decrement in LT50 f SE was 11.2 + 0.6 d; for ten resistant strains, the mean decrement was 5.1 f 0.8 d; for the remaining 5 strains, which could not be unambiguously classified as sensitive to RLD, the mean decrement was 8.6 + 1.1 d. Strains homozygous for whole chromosomes (either X or one of the two large autosomes) exhibited continuous variation for sensitivity to clock shifting. No chromosome accounted for a disproportionate share of the variation, suggesting a multigenic basis for this phenotype. The LT50 in a normal, constant light-dark regime (CLD) ranged from 31.7 d to 65.3 d, with chromosome 2 contributing most heavily to this variation. The correlation between LT50 and percent decrement in LT50 was not significant (r = .23, df = 21, P > .20). In most sensitive strains, RLD and CLD groups did not begin to differ in percent surviving until after .5 of CLD LT50; after this critical point, RLD animals started dying at a n increased rate. RLD may be stressful by disrupting temporal organization of physiological processes immediately following phase shifts, during the period marked by transients in observed phase response.