The effect of heavy metals on sugar transport in fully resting guinea pig left atria was studied by measuring the tissue-medium distribution of 3-methylglucose. Basal sugar transport was increased significantly by all heavy metals tested (Co2+, Ni2+, Zn2+, Mn2+ (2 mM) and by La3+ (0.05 mM) but 1 mM La3+ had no effect. The stimulation of sugar transport by insulin, hyperosmolarity, K+-free medium, or 10(-5) M ouabain was strongly antagonized by Ni2+, Zn2+, and La3+ but was unaffected by Co2+ and Mn2+. The heavy metals did not affect intracellular Na2+ and K+, whether in the basal state or when the Na+ pump was depressed by ouabain or K+-free medium. The data suggest that Ca2+ antagonistic ions may affect sugar transport both by inhibiting Ca2+ influx and by competing with Ca2+ for specific binding sites presumably involved in the regulation of sugar transport.