Drosophila mutants with defects in their proboscis extension reflex (PER) were isolated for a genetic dissection of the PER system. Five mutant strains were screened from 35,000 mutagenized flies through a twostep screening: a mass test of sugar intake, followed by an individual PER test. Mutants were classified into three complementation groups: aperA (genetical map position, 1–22.1), aperB (1–0.6) and aperC (1–0.4). The aperA mutants showed incomplete penetrance and expressivity. Some flies did not extend their proboscises at all, while others did so only to either the right or the left side; the PERs of the rest were apparently normal. The aperB mutants showed abnormality in the direction of the PER: they extended their proboscises backward, instead of straight forward. The aperB mutation was temperature-sensitive and its phenotype was expressed at a culture temperature above 25°C. The aperC mutation caused a PER defect in aged flies. Within 2 days of eclosion they showed normal PER, but 2 or more days after eclosion most of them had become unable to extend their proboscises. Later, about half of the aperC mutants recovered the PER ability. The anatomical site of action of these mutations seems to be in the neuromuscular or skeletomuscular system.