Abstract: Tablets were dissolved in water, sedimented and filtered. Portions of the filtrate were injected into a water carrier stream (0.67 ml/min) which mixed with a reagent comprising aqueous 4-aminophenazone, di-sodium EDTA buffer of pH 10 and 1% Brij 35 at 0.54 ml/min in a coil prior to reaction with potassium hexacyanoferrate(III) (0.54 ml/min) in a second coil at ambient temperature The absorbance of the dye formed was measured at 520 nm. A modified simplex method was employed to optimize several mutually affected variables and individual variables (tabulated), including the lengths of the coils used and the concentrations of reagents. Calibration graphs (peak height) were linear (r 0.995) for 1-20 and 20-250 mg/l of doxycycline, oxytetracycline, rolitetracycline and tetracycline with RSD of 1% for 10 and 100 mg/l and an output of 60-70 samples/h.