To prepare fluorescent zinc sensors with binding affinities lower than that of the parent 9-(o-carboxyphenyl)-2,7-dichloro-4,5-bis(bis(2-pyridylmethyl)methylamino methyl)-6-hydroxy-3-xanthenone (ZP1), dimethylated and tetramethylated derivatives were synthesized having either two or four of the pyridyl subunits methylated at the 6-position. Like the parent ZP1, both Me(2)ZP1 and Me(4)ZP1 exhibit increased fluorescence in the presence of Zn2+. The integrated emission of Me(2)ZP1 increases 4-fold in the presence of excess zinc, whereas Me(4)ZP1 displays 2.5-fold enhanced fluorescence for Zn2+. Methylating the 6-positions of the pyridyl rings raises the dissociation constant of the sensors and lowers the pK(a) values associated with the tertiary amine ligands in a systematic manner. The properties of the dimethylated Me(2)ZP1 dye resemble those of ZP1, but the tetramethylated Me(4)ZP1 differs greatly from ZP1 in terms of its brightness, affinity toward Zn2+, exchange kinetics, and metal sensitivity. Both Me(2)ZP1 and Me(4)ZP1 can enter HeLa cells and signal the presence of Zn2+. Staining caused by both dyes is punctate, with localization patterns resembling that observed for ZP1.