The inhibition of wheat Ca(2+)-dependent protein kinase (CDPK) by substituted acridines and substituted 5-, 6-, 7- and 8-azaacridines (5-AA, 6-AA, 7-AA and 8-AA) was examined. Of a total of 71 substituted acridines and azaacridines examined, only 20 have IC50 values for wheat CDPK of less than 200 microM. Of these, effective compounds all have neutral or basic 4-substituents, except for 2,7-dibromo-4-carboxy-5-AAO (IC50 73 microM), the carboxymethyl ester of which is a much better inhibitor (IC50 20 microM). There is a large aza position effect so that various 4-substituted azaacridines can be either very active or very poor inhibitors depending upon the azaacridine nucleus substituted. One of the most potent inhibitors found is the 8-AA 4-N-(2-dimethylaminoethyl)carboxamide (4-P) derivative (IC50 1.5 microM), but the corresponding 4-substituted acridine analogue is a very poor inhibitor. Other potent inhibitors found include 1-nitro-4-P-8-AA (IC50 4 microM) and 7-bromo-4-methyl-5-AA (IC50 0.7 microM). These potent and relatively specific CDPK inhibitors may be useful in obtaining evidence for CDPK involvement in plant cell responses to specific signals.