Background Anesthesia and sleep share physiologic and behavioral similarities. The anesthetic requirement of the recently identified Drosophila mutant minisleeper and other Drosophila mutants was investigated. Methods Sleep and wakefulness were determined by measuring activity of individual wild-type and mutant flies. Based on the response of the flies at different concentrations of the volatile anesthetics isoflurane and sevoflurane, concentration-response curves were generated and EC50 values were calculated. Results The average amount of daily sleep in wild-type Drosophila (n = 64) was 965 +/- 15 min, and 1,022 +/- 29 in Na[har](P > 0.05; n = 32) (mean +/- SEM, all P compared to wild-type and other shaker alleles). Sh flies slept 584 +/- 13 min (n = 64, P < 0.01), Sh flies 412 +/- 22 min (n = 32, P < 0.01), and Sh flies 782 +/- 25 min (n = 32, P < 0.01). The EC50 values for isoflurane were 0.706 (95% CI 0.649 to 0.764, n = 661) and for sevoflurane 1.298 (1.180 to 1.416, n = 522) in wild-type Drosophila; 1.599 (1.527 to 1.671, n = 308) and 2.329 (2.177 to 2.482, n = 282) in Sh, 1.306 (1.212 to 1.400, n = 393) and 2.013 (1.868 to 2.158, n = 550) in Sh, 0.957 (0.860 to 1.054, n = 297) and 1.619 (1.508 to 1.731, n = 386) in Sh, and 0.6154 (0.581 to 0.649, n = 360; P < 0.05) and 0.9339 (0.823 to 1.041, n = 274) in Na[har], respectively (all P < 0.01). Conclusions A single-gene mutation in Drosophila that causes an extreme reduction in daily sleep is responsible for a significant increase in the requirement of volatile anesthetics. This suggests that a single gene mutation affects both sleep behavior and anesthesia and sedation.