OBJECTIVE An excess of toxic trace elements or a deficiency of essential ones has been implicated in many common diseases or public health problems, but little is known about causes of variation between people living within similar environments. We estimated effects of personal and socioeconomic characteristics on concentrations of arsenic (As), cadmium (Cd), copper (Cu), mercury (Hg), lead (Pb), selenium (Se), and zinc (Zn) in erythrocytes and tested for genetic effects using data from twin pairs. METHODS We used blood samples from 2,926 adult twins living in Australia (1,925 women and 1,001 men; 30-92 years of age) and determined element concentrations in erythrocytes by inductively coupled plasma-mass spectrometry. We assessed associations between element concentrations and personal and socioeconomic characteristics, as well as the sources of genetic and environmental variation and covariation in element concentrations. We evaluated the chromosomal locations of genes affecting these characteristics by linkage analysis in 501 dizygotic twin pairs. RESULTS Concentrations of Cu, Se, and Zn, and of As and Hg showed substantial correlations, concentrations of As and Hg due mainly to common genetic effects. Genetic linkage analysis showed significant linkage for Pb [chromosome 3, near SLC4A7 (solute carrier family 4, sodium bicarbonate cotransporter, member 7)] and suggestive linkage for Cd (chromosomes 2, 18, 20, and X), Hg (chromosome 5), Se (chromosomes 4 and 8), and Zn {chromosome 2, near SLC11A1 [solute carrier family 11 (proton-coupled divalent metal ion transporters)]}. CONCLUSIONS Although environmental exposure is a precondition for accumulation of toxic elements, individual characteristics and genetic factors are also important. Identification of the contributory genetic polymorphisms will improve our understanding of trace and toxic element uptake and distribution mechanisms.