Howl appears to be a sprawling, disorganized poem. But it's not. It consists of three sections. Each of these sections is a prolonged "riff" on a single subject. You could even think of the poem as three enormous run-on sentences. The first section is by far the longest.
In the first line of the first section, the speaker tells us that he has been a witness to the destruction of "the best minds" of his generation. The rest of the section is a detailed description of these people – specifically, who they were and what they did. He doesn't tell us what destroyed them quite yet, though we get plenty of hints. Most lines begin with the word "who" followed by a verb. These are people "who did this, who did that," etc. We quickly learn that these "best minds" were not doctors, lawyers, and scientists. They were not people whom most middle-class folks in the 1950s would have identified with the best America had to offer. And that's exactly Ginsberg's point. According to the speaker, they are drug users, drop outs, world travelers, bums, musicians, political dissidents, and, yes, poets.
If the key word of the first section was "who," the second section asks "What?" As in, what destroyed the best minds of his generation? Ginsberg provides the answer immediately: Moloch. In the Hebrew Bible, Moloch was an idolatrous god to whom children were sacrificed by placing them in fire. In other words, not a friendly god. The religious context and history of Moloch is extremely complicated, so it's better to stick to the poem's own definition. For Ginsberg, Moloch is associated with war, government, capitalism, and mainstream culture, all of which might be summed up by one of the poem's most important concepts: the "machine" or "machinery." Moloch is an inhuman monster that kills youth and love.
The third section is addressed to Carl Solomon, Ginsberg's close friend from the Columbia Presbyterian Psychiatric Institute. The speaker refers to this psychiatric hospital by the shorter and more evocative fictional name of "Rockland." He reaffirms his solidarity with Solomon over and over again by repeating the phrase "I'm with you in Rockland." The central question of this section is "Where?" The speaker uses this question to explore Solomon's existence within the walls of the institute. The poem ends with the image from the speaker's dreams, in which Solomon is walking from New York to the speaker's "cottage" (in Berkeley, California), where they will reunite.