Abstract Objective This study aims to clarify the relationship between blood Pb2+ concentration as a ubiquitous environmental pollutant and plasma neurotransmitters as biochemical parameters that reflect brain function in Saudi autistic patients. Methods RBC's lead content together with plasma concentration of gamma aminobutyric acid (GABA), serotonin (5HT) and dopamine (DA) were measured in 25 Saudi autistic patients and compared to 16 age-matching control samples. Results The obtained data recorded that Saudi autistic patients have a remarkable higher levels of Pb2+ and significantly elevated levels of GABA, 5HT and DA compared to healthy subjects. ROC analysis revealed satisfactory values of specificity and sensitivity of the measured parameters. Conclusion This study suggests that postnatal lead toxicity in autistic patients of Saudi Arabia could represent a causative factor in the pathogenesis of autism. Elevated GABA, 5HT and DA were discussed in relation to the chronic lead toxicity recorded in the investigated autistic samples.