Dietary deficiency of trace metals among human populations, once thought to be exceedingly rare, has recently gained attention as a potential public health problem. The consumption of highly refined and heavily processed foods reduces the trace element content of the diet. The higher trace element requirements of pregnancy, lactation, growth, development, and chronic disease may further contribute to states of marginal trace metal nutriture. Experimental animal studies have demonstrated that even marginal trace element deprivation during critical periods of growth and development or, alternately, during prolonged deficiency in adults can significantly alter immunologic function. Furthermore, trace metal nutriture has been shown to affect initiation and progression of a large variety of neoplasia. Studies of the interaction of trace metal nutriture and cancer have, however, suffered from many methodological inconsistencies as well as failures to define and quantitate the trace element content of diets and the host alterations in response to neoplastic challenge. Similarly, there has been little information in the critical area of marginal and moderate trace metal deficiency, i.e., those experimentaL situations most analogous to deficiencies that may occur in human populations. In this review, an attempt is made first to place in perspective experimental data relevant to these issues, and second to emphasize the desirability of further investigation in this critical area of human nutrition.