Current working conditions and new forms of work organization are affecting workers’ health in numerous way wich can only be explained by more complex theories and methodologies than those used traditionally. The authors analyze some important elements of the work process and the interaction among work demands as determinants of mental and psychosomatic disorders and fatigue (MPDF) among workers in a Mexican industrial plant. The workers studied (n=830) were male, with a mean age of 32. MPDF represent one-third of the disease burden among these workers. An association was observed with the number of years worked, type of activity, and job area. Job-related demandas and work organization, including excessive work, strict supervision, dangerous work, unnatural positions, and intense and hard physical labor were also closely related to these conditions. The most relevant problem is the combination of many different demands. Interaction among the combinations was found to be additive or synergistic. In the latter condition the risk of morbid effects increases beyond merely and additive effect.