Abnormal physiological responses of plant cultures such as shoot tip necrosis, callus, and hyperhydricity are some of the most difficult challenges in shoot micropropagation, and their causes are not well understood. Five Murashige and Skoog mineral salt factors, which influence the growth of pear shoot cultures, were tested in a five-dimensional surface response experimental design. Pyrus communis ‘Old Home × Farmingdale 87,’ ‘Horner 51,’ and ‘Winter Nelis’; Pyrus dimorphophylla; and Pyrus ussuriensis ‘Hang Pa Li’ shoot cultures were grown on 43 computer-designed treatments to represent the design space of all possible treatment combinations. Analysis of shoot response to these treatments identified the factors that both contributed to physiological disorders and remedied them. Undesirable callus formation was common for pear shoots cultured on standard medium and decreased on formulations with increased NH 4NO 3, Fe, and mesos (CaCl 2, KH 2PO 4, and MgSO 4) for most genotypes. Shoot tip necrosis varied with the genotype, but low mesos or low nitrogen concentrations contributed to the necrosis. Hyperhydricity was more prominent with low mesos or low NH 4NO 3. Hooked and upwardly curled new leaves were seen in most genotypes and resulted from use of low mesos in P. communis and low nitrogen for ‘Hang Pa Li’ and P. dimorphophylla. Fasciation and hypertrophy were seen infrequently and resulted from wide imbalances in several nutrients simultaneously. In general, standard concentrations of Murashige and Skoog iron and micros combined with high mesos and moderate nitrogen compounds produced normal shoots without physiological disorders. [ABSTRACT FROM AUTHOR]