Experimental lesions and quantitative autoradiography were used to investigate the cellular distribution of neurotransmitter receptors in rats. Lesions were produced by intracortical injections of either volkensin or ricin. However, only the former is retrogradely transported and volkensin treatment causes significant loss of contralateral cortical pyramidal neurones. Binding of [3H]pirenzepine (muscarinic M1 receptors) and [3H]nicotine was reduced in contralateral cortex in volkensin compared with ricin and/or control (uninjected) animals. However, binding of [3H]8-hydroxy-2-(n-dipropylamino)tetralin (5-HT1A receptors), [3H]ketanserin (5-HT2A receptors), and [3H]1,3-dipropylcyclopentylxanthine (adenosine A1 receptors) was unchanged. The most likely explanation for these results is that M1 and nicotinic receptors are present in large numbers on those pyramidal neurones that are lost. The results are discussed in terms of the biology of cortical pyramidal neurones, drugs for Alzheimer's disease, and novel ligands for improving human brain scanning techniques.