Seen in perspective, it is evident that lead poisoning is one of the earliest occupational diseases, described already thousands of years ago. The first major upswing in the history of anthropogenic production of lead was associated with the development of the Greco-Roman culture and the most recent followed the Industrial Revolution. At the peak of the power of the Roman Empire, lead production was about 80,000 tons per year, lead and its compounds were used with great inventiveness in numerous ways, and lead poisoning was pandemic, with the severity of poisoning proportional to the power and status of the class. Intake of lead by the aristocracy may have been as much as 1 mg/day. The resultant mental incompetence and especially the rapidly declining birth rate among the ruling class are now believed to have been major factors in the decline of the Roman Empire. Epidemic outbreaks of lead poisoning have occurred repeatedly throughout history and still occur today. The estimated 3.5 million tons of lead produced annually during peak production in the 1970's included about 0.4 million tons of organoleads. Such intense production has increased global contamination with lead enormously. Even under relatively ideal conditions the daily intake of lead is so much higher than in prehistoric times that investigators must pause to ask themselves what a proper control group really is. Are investigators merely determining the effects of additional lead exposure on systems already greatly perturbed by lead? If so, how can we find out?