In this study, we assessed the potential for the development of resistance to the insecticide spinosad in a laboratory colony of the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). Resistance was selected by using topical applications of spinosad. After eight generations of selection, the LD₅₀ of the selected line was 408 times greater compared with that of the untreated parental colony. This spinosad-resistant line did not exhibit cross-resistance to 10 other insecticides tested, including six organophosphates (naled, trichlorfon, fenitrothion, fenthion, formothion, and malathion) one carbamate (methomyl), and three pyrethroids (cyfluthrin, cypermethrin, and fenvalerate). However, using lines previously selected for resistance to these same insecticides, two of the 10 lines tested (naled- and malathion-resistant) did show some cross-resistance to spinosad. Also, oriental fruit flies from different field collections where naled and malathion have been used for control purposes displayed some resistance to spinosad. In addition, the effects of direct ingestion of spinosad through dietary supplementation also were tested. Overall, the laboratory resistance and cross-resistance data developed in this study provide new information that will be useful for managing the development of resistance when spinosad is used to control B. dorsalis in the field.