The clinical spectrum of acrodermatitis enteropathica (n = 226) is compared with symptoms reported in other Zn deficiencies: total parenteral nutrition without Zn (n = 21), protein energy malnutrition (n = 24), gastrointestinal disease (n = 79), geophagia (n = 227), and dietary low intake (n = 23). Common features of deficiency are diarrhea, recurrent infection, and growth retardation. Dermatitis is less common in other types of deficiency than in acrodermatitis enteropathica (9 vs 88% of cases). Anorexia and/or hypogeusia is reported more frequently in the other types of deficiency (30 vs 16%). The main symptoms in acrodermatitis enteropathica vary with age. These differences in the clinical picture of Zn deficiency are discussed in relation to the degree of the deficiency (acute, subacute, or chronic; severe, mild, or subclinical). The results of the conventional laboratory tests to diagnose Zn deficiency (Zn levels in serum, urine, or hair) are reviewed. In healthy Dutch infants and children, the mean values of these levels vary by a factor of 1.6-3.0. Also, the clinical interpretation of their results is prone to errors. Therefore, we advocate the erythrocytic 65Zn uptake test. Its mean varies by 1.3. However, its reference values for different age intervals need to be established. From the comparison of the results of three conventional tests of samples taken concurrently (serum, urine, and hair) in groups of Dutch children with symptoms common in Zn deficiency (diarrhea, recurrent infection, or growth retardation), it is estimated that +/- 1% of Dutch children with minor complaints suffer from either acute or subacute Zn deficiency. Other deficiencies occur occasionally. In order to detect the individual patient with deficiency, the erythrocytic 65Zn uptake test is promising and needs to be evaluated. Therefore, we review a set of reference laboratory tests with results that alter during sequential stages of overload and deficiency. Such a scheme is advocated as a guidance for future clinical research on deficiency, and solves the problem of differentiating those conditions that identify the individual patients who need treatment by supplementation.