| Summary: | <i>Musca domestica</i> L., the common house fly, is a cosmopolitan carrier of human and livestock disease pathogens. The species exhibits resistance to many insecticides; therefore, effective <i>M. domestica</i> insecticide resistance management programs are required worldwide. In the present study, the development of alpha-cypermethrin resistance, realized heritability (<i>h</i><sup>2</sup>), instability of resistance trait (DR), and cross-resistance (CR) was investigated in an alpha-cypermethrin-selected <i>M. domestica</i> strain (Alpha-Sel) across 24 generations (Gs). Compared with an alpha-cypermethrin-unselected strain (Alpha-Unsel), resistance to alpha-cypermethrin increased from 46.4-fold (G<sub>5</sub>) to 474.2-fold (G<sub>24</sub>) in Alpha-Sel females and 41.0-fold (G<sub>5</sub>) to 253.2-fold (G<sub>24</sub>) in Alpha-Sel males. Alpha-cypermethrin resistance declined by between –0.10 (G<sub>5</sub>) and –0.05 (G<sub>24</sub>) in both <i>M. domestica</i> sexes without insecticide exposure for 24 generations. The <i>h</i><sup>2</sup> of alpha-cypermethrin resistance was 0.17 and 0.18 for males and females, respectively, in G<sub>1</sub>–G<sub>24</sub>. With selection intensities of 10–90%, the G values required for a tenfold increase in the LC<sub>50</sub> of alpha-cypermethrin were 6.3–53.7, 4.1–33.8, and 3.0–24.7, given <i>h</i><sup>2</sup> values of 0.17, 0.27, and 0.37, respectively, and a constant slope of 2.1 for males and <i>h</i><sup>2</sup> values of 0.18, 0.28, and 0.38, respectively, and a constant slope of 2.0 for females. Compared with Alpha-Unsel, Alpha-Sel <i>M. domestica</i> exhibited moderate CR to bifenthrin (15.5-fold), deltamethrin (28.4-fold), and cyfluthrin (16.8-fold), low CR to two pyrethroids and five organophosphates, and no CR to insect growth regulators. The instability of resistance trait, low <i>h</i><sup>2</sup>, and absent or low CR associated with alpha-cypermethrin resistance in <i>M. domestica</i> indicate resistance could be managed with rotational use of the insecticide.
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