A very sensitive analytical method is proposed for the determination of lithium based on the reaction of Li(+) ion with 1,4-dihydroxyanthraquinone (Quinizarin). In dimethylsulfoxide medium (90%) and in the presence of sodium hydroxide and sodium carbonate, a bluish-violet color (lambda(max) = 601 nm) develops and is stable over a period of 30 min to 2.5 h. The NaOH and Quinizarin concentrations were optimized simultaneously using the response surface methodology from sequential experimental Doehlert designs. Beer's law is obeyed in the concentration range 14-250 ppb Li(+) in aqueous and serum matrices, and the errors (RSD) in the determination of 100 ppb Li(+) are 4.0% and 3.9% respectively. The proposed procedure was satisfactorily applied to the determination of lithium in drugs and human serum (no deproteinization is required).