Effects of temperature, relative humidity, and light on MSMA phytotoxicity to wild-type and arsenical herbicide-resistant biotypes of common cocklebur grown from seed collected in Mississippi were evaluated. In growth chamber studies, 20-d-old plants were sprayed with 0.5 kg ai/ha of MSMA, and after 7 d, fresh weight and chlorophyll content were measured to estimate phytotoxicity. All three environmental factors influenced the level of weed resistance. In studies with day/night temperatures of 30/25 C and 500 μmol/m2/s PPFD light with a 14-h photoperiod, phytotoxicity of MSMA at 40% relative humidity was minimal, but was significantly greater at 60 and 90% relative humidities. The resistant (R) biotype was affected less than the susceptible (S) biotype at the higher relative humidities. The level of resistance estimated by fresh weight reduction was greatest at 30/25 C, but was most pronounced at 35/30 C using chlorophyll measurements. Resistance was lowest at 25/20 C by either measurement. MSMA phytotoxicity occurred at light intensities of 75, 500, and 750 μmol/m2/s PPFD; however, biotypic response was greatest at 500, followed by 750 μmol/m2/s PPFD. Resistance of the (R) biotype to MSMA was not significant at 75 μmol/m2/s, suggesting that differentiation between the biotypes for MSMA sensitivity would be difficult under low light.