Green tobacco sickness (GTS) is an occupational illness that affects tobacco workers worldwide. This study tested whether GTS results from nicotine poisoning. Data collection was based on a prospective design in which 182 farmworkers were interviewed up to five times at biweekly intervals. A saliva sample was obtained at each interview. Examining four regression models in which salivary cotinine was evaluated as a mediator between behavioral risk factors and GTS, this analysis showed that nicotine causes GTS: 25 workers had 31 occurrences of GTS. Among nonsmokers, each increment increase in the natural log of cotinine increased the odds of GTS 2.11 times, adjusting for task and wet conditions. Treatment of GTS must address nicotine poisoning. GTS affects laborers with limited resources. Research must disclose the extent of this occupational illness and investigate ways to prevent it.