A new capillary zone electrophoresis (CZE) method for the determination of tacrine (THA), 7-methoxytacrine (7-MTHA) and their basic metabolites (THAm, 7-MTHAm) in pharmaceutical and biological samples (urine and serum) was developed. Separation of all compounds by CZE was carried out using a 46.6 cm untreated fused-silica capillary applying 20 kV separation voltage using 50 mM phosphate buffer of pH 2.8 for THA and THAm and of pH 7.8 for 7-MTHA and 7-MTHAm as background electrolyte (BGE). Detection was carried out at 240 nm (THA and THAm) and 248 nm (7-MTHA and 7-MTHAm). THA and THAm were separated in less than 4 min while 7-MTHA and 7-MTHAm were separated in less than 7 min. The detection limits (SIN = 3) obtained were 3 ppb for THA and 4 ppb for 7-MTHA in aqueous solutions; 50 ppb for THA and 47 ppb for 7-MTHA for the determination in urine (diluted 1:10); 52 ppb for THA and 56 ppb for 7-MTHA, in deproteinized serum samples. The methods are suitable for therapeutic drug monitoring of the drugs.