The hypothesis that a large, possibly toxic, increase in cellular calcium accompanies photoreceptor cell degeneration in several different Drosophila mutants was tested. The calcium content of wild type and mutant photoreceptors of Drosophila was measured using rapid freezing of the eyes and energy-dispersive x-ray analysis (e.d.x.) of cryosections and semithin sections of cryosubstituted material. Light- and dark-raised mutants of the following strains were studied: retinal degeneration B (rdgB); retinal degeneration C (rdgC); neither inactivation nor afterpotential C (ninaC), and no receptor potential A (norpA). These are light-dependent retinal degeneration mutants in which the affected gene products had been previously shown as myosin-kinase (ninaC), calcium-dependent phosphoprotein phosphatase (rdgC), phosphoinositide transfer protein (rdgB), and phospholipase C (norpA). In light-raised mutants, ommatidia of variable degrees of degeneration were observed. Mass-dense globular bodies of 200–500 nm diameter in relatively large quantities were found in the degenerating photoreceptor of all the mutants tested. These subcellular globules were found to have a very high calcium content, which was not found in wild type or in nondegenerating photoreceptors of the mutants. Nondegenerating photoreceptors were found not only in dark-raised mutants, but in smaller quantities also in light-raised mutants. Usually these globular structures contained high levels of phosphorus, indicating that at least part of the calcium in the mutant photoreceptors is precipitated as calcium phosphate. The results indicate that a large increase in cellular calcium accompanies light-induced photoreceptor degeneration in degenerating Drosophila mutants even when induced by very different mutations, suggesting that the calcium accumulation is a secondary rather than a primary effect in the degeneration process.