Profenofos, tradename Curacron, an organophosphate insecticide - miticide, can cause various responses in cotton ranging from leaf reddening or spotting to total necrosis and abscission. These responses are often erratic and difficult to predict. This study was conducted to examine the relationship between droplet size and leaf spotting or reddening. Stoneville 825 was treated in a spray chamber, five weeks after seeding in a growth chamber, using four spray tips (TX3, TX4, TX6, and 650067) to produce different droplet sizes. Each spray tip was calibrated to deliver 3.0 GPA. Water sensitive papers were used to determine droplet size. The uppermost fully expanded leaf at treatment exhibited most of the response (primarily necrotic spotting) when rated one week after treatment. The addition of Prime Oil to profenofos increased leaf spotting compared to profenofos used alone or in combination with cottonseed oil (3.2% vs. 0.6% and 0.7%, respectively). No relationship between droplet size and leaf spotting for profenofos used in combination with cottonseed oil was detected. A linear increase in leaf spotting as droplet size increased was detected for profenofos used alone. A quadratic response was observed for profenofos used with Prime Oil, with spotting generally increasing as droplet size increased; however, the highest ratings were not associated with the largest droplets. The data suggests that droplet size should not exceed 300 µm in order to minimize leaf spotting. The addition of cottonseed oil to profenofos to reduce leaf spotting also appears beneficial under a wide range of droplet sizes.