<p>Plackett-Burman and Quarter fraction 2^5-2 factorial designs were applied to evaluate a spectrophotometric flow injection method in order to determine phenol in water by using 4-aminoantipyrine (4-aap) as derivatizing reagent. With a minimum number of experiments, the designs enabled the best conditions for phenol analysis: 80 cm and 180 cm reactors; flow-rates being: NH₃ 1.0 mL min^-1; 4-aap 0.35 mL min^-1 and K₃[Fe(CN)₆] 0.35 mL min^-1, [NH₃] 0.064 mol L^-1, [4-aap] 9.84 × 10−3 mol L^-1, [K₃[Fe(CN)₆]] 0.02 mol L^-1, and an injection volume of 200 μL. With the optimized method it was possible to increase the lineal range from 0.3 μg mL^-1 to 30 μg mL^-1 and also to quantify the maximum allowable phenol concentration in water in comparison with other standard and flow injection methods whose lineal range are from 0.5 μg mL^-1 to 20 μg mL^-1 and from 0.5 μg mL^-1 to 16 μg mL^-1, respectively. The detection limit was of 0.13 μg mL^-1 and the regression coefficient was of 0.9999, making possible a throughput of 36 determinations an hour with a minimum consume of reagent. With the proposed method, a distillation step was not necessary to remove sulfates but, when the sulfate:phenol ratio was higher than 83, the analytical signal for phenol increased 8%, but hypochlorite interfered with the signal when the ypochlorite:phenol ratio was higher than 1.</p>